DESCRIPTION: Three specific aims are proposed that will address these important unresolved issues. 1) The mechanism by which NGF induced phosphorylation of Elk-1 and CREB triggers c-fos transcription will be investigated. 2) The role that phosphorylation and protein: protein interactions play in regulating the CREB kinase will be characterized. 3) The importance of the ERKS and Elk-1, and CREB kinase and CREB as mediators of neuronal differentiation and survival will be explored. Given the critical role that NGF plays in nervous system development and the important of IEGs in the control of cell growth and differentiation, the proposed experiments have the potential to give new insight into how the deregulation of these processes can lead to neural degeneration or oncogenesis.